Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia.

BACKGROUND: Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3). OBJECTIVES: We aim to comprehensively investigate CA8-related disorders (CA8-RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients. METHODS: We analyzed the phenotype of 27 affected individuals from 14 families with biallelic CA8 variants (including data from 15 newly identified patients from eight families), ages 4 to 35 years. Clinical, genetic, and radiological assessments were performed, and zebrafish models with ca8 knockout were used for functional analysis. RESULTS: Patients exhibited varying degrees of neurodevelopmental disorders (NDD), along with predominantly progressive cerebellar ataxia and pyramidal signs and variable bradykinesia, dystonia, and sensory impairment. Quadrupedal gait was present in only 10 of 27 patients. Progressive selective cerebellar atrophy, predominantly affecting the superior vermis, was a key diagnostic finding in all patients. Seven novel homozygous CA8 variants were identified. Zebrafish models demonstrated impaired early neurodevelopment and motor behavior on ca8 knockout. CONCLUSION: Our comprehensive analysis of phenotypic features indicates that CA8-RD exhibits a wide range of clinical manifestations, setting it apart from other subtypes within the category of CAMRQ. CA8-RD is characterized by cerebellar atrophy and should be recognized as part of the autosomal-recessive cerebellar ataxias associated with NDD. Notably, the presence of progressive superior vermis atrophy serves as a valuable diagnostic indicator. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neutralizing the surging emissions amidst natural resource dependence, eco-innovation, and green energy in G7 countries: Insights for global environmental sustainability.

The unrelenting surge in global warming in the current era suggests the inevitable need for governments across the globe to embark on policy measures that will help flatten the curve of the surging emissions. Consequently, the concept of carbon neutrality has become a vital policy approach for countries to achieve sustainable development. The present study extends the debates on carbon neutrality by examining the extent to which prominent factors such as natural resource dependence, eco-innovation, and green energy (biofuel and renewable energy) facilitate or hinder strides toward achieving carbon neutral environment in G7 economies. The study considers the additional roles of carbon tax, environmental policy stringency, and financial development in longitudinal data ranging from 1997 to 2019. The verification of the stated hypotheses hinges on a battery of estimators comprising cross-sectional ARDL, common correlated effects mean group, augmented mean group, and panel quantile regression. The empirical findings show that green energy, carbon tax, and environmental policy support the drive towards carbon neutrality by reducing the stock of CO2 emissions. On the other hand, natural resource dependence and financial development hinder the carbon neutrality agenda by escalating the surge in CO2 emissions. Robustness analyses are conducted from the angle of an additional outcome variable and estimation technique of which the results corroborate the empirical regularity of the main findings. Policy implications are derived from the empirical findings.

Comparative evaluation of ethyl acetate and n-Hexane extracts of Cannabis sativa L. leaves for muscle function restoration after peripheral nerve lesion.

Peripheral nerve injuries are one of those complex medical conditions for which a highly effective first-line treatment is currently missing. The use of natural compound as medicines to treat various disorders has a long history. Our previous research explored that crude Cannabis sativa L. accelerated the recovery of sensorimotor functions following nerve injury. The purpose of the current study was to investigate the effects of n-Hexane and ethyl acetate extracts of C. sativa L. leaves on the muscle function restoration in a mouse model after sciatic nerve injury. For this purpose, albino mice (n = 18) were equally divided into control and two treatment groups. The control group was fed on a plain diet while treatment groups were given a diet having n-Hexane (treatment 1) and ethyl acetate (treatment 2) extracts of C. sativa L. (10 mg/kg body weight), respectively. The hot plate test (M = 15.61, SD = 2.61, p = .001), grip strength (M = 68.32, SD = 3.22, p < .001), and sciatic functional index (SFI) (M = 11.59, SD = 6.54, p = .012) assessment indicated significant amelioration in treatment 1 as compared to treatment 2 group. Furthermore, muscle fiber cross-sectional area revealed a noticeable improvement (M = 182,319, SD = 35.80, p = .013) in treatment 1 while muscle mass ratio of Gastrocnemius (M = 0.64, SD = 0.08, p = .427) and Tibialis anterior (M = 0.57, SD = 0.04, p = .209) indicated nonsignificant change. A prominent increase in total antioxidant capacity (TAC) (M = 3.76, SD = 0.38, p < .001) and momentous decrease in total oxidant status (TOS) (M = 11.28, SD = 5.71, p < .001) along with blood glucose level indicated significant difference (M = 105.5, SD = 9.12, p < 0.001) in treatment 1 group. These results suggest that treatment 1 has the ability to speed up functional recovery after a peripheral nerve lesion. Further research is necessary, nevertheless, to better understand the extract's actual curative properties and the mechanisms that improve functional restoration.

Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets.

Axons in the peripheral nervous system have the ability to repair themselves after damage, whereas axons in the central nervous system are unable to do so. A common and important characteristic of damage to the spinal cord, brain, and peripheral nerves is the disruption of axonal regrowth. Interestingly, intrinsic growth factors play a significant role in the axonal regeneration of injured nerves. Various factors such as proteomic profile, microtubule stability, ribosomal location, and signalling pathways mark a line between the central and peripheral axons' capacity for self-renewal. Unfortunately, glial scar development, myelin-associated inhibitor molecules, lack of neurotrophic factors, and inflammatory reactions are among the factors that restrict axonal regeneration. Molecular pathways such as cAMP, MAPK, JAK/STAT, ATF3/CREB, BMP/SMAD, AKT/mTORC1/p70S6K, PI3K/AKT, GSK-3ß/CLASP, BDNF/Trk, Ras/ERK, integrin/FAK, RhoA/ROCK/LIMK, and POSTN/integrin are activated after nerve injury and are considered significant players in axonal regeneration. In addition to the aforementioned pathways, growth factors, microRNAs, and astrocytes are also commendable participants in regeneration. In this review, we discuss the detailed mechanism of each pathway along with key players that can be potentially valuable targets to help achieve quick axonal healing. We also identify the prospective targets that could help close knowledge gaps in the molecular pathways underlying regeneration and shed light on the creation of more powerful strategies to encourage axonal regeneration after nervous system injury.

Vitamin C supplementation ameliorates liver function profile and antiviral treatment response in Hepatitis C patients.

An imbalance between oxidative stress and antioxidative defence mediates a variety of diseases pathogenesis. The present study aims to assess the possible outcome of supplementation of oral vitamin-C (VC), an antioxidant, in Viral Hepatitis C (HCV) treatment as an adjuvant therapy. 200 HCV-patients were selected, 100 were given Vitamin-C (1000 mg/day) along with anti HCV treatment (sofosbuvir plus daclatasvir) while the other 100 took only anti-HCV treatment for 4weeks. The serum ascorbic acid (Vitamin-C) levels and functions of the liver were tested before and after the VC supplementation. HCV patients with relatively low serum ascorbic acid showed significant improvement after the intake of vitamin C. After 4 weeks of treatment, AST, ALP, albumin, and total, direct and indirect bilirubin were improved significantly in the VC group; whereas only ALT and indirect bilirubin were improved in both groups when associated with the control subjects. Comparing the two treatment groups at 4weeks; more effective and significant improvement was observed in ALT (p<0.01), AST (p<0.001), direct (p<0.01) and indirect bilirubin (p<0.001), total proteins (p<0.001) and albumin (p<0.05) in patients with VC supplementation on anti-viral treatment compared to only anti-viral treatment group. Thus, VC supplementation improves the antiviral therapy outcome by bestowing a beneficial effect in minimizing liver damage in HCV cases.

Investigating the existence of asymmetric environmental Kuznets curve and pollution haven hypothesis in China: Fresh evidence from QARDL and quantile Granger causality.

This study aims to analyze the asymmetric long-run relationship between economic growth (EG), foreign direct investment (FDI), and carbon emissions (CO2) within the context of the environmental Kuznets curve (EKC) and the pollution haven hypothesis (PHH) in China. Employing the quarterly data from 1982Q1 to 2018Q4, we have used novel techniques to meet the stated objectives of our study, named quantile ARDL and quantile Granger causality. The study provides novel outcomes using the advanced quantile ARDL and quantile Granger causality tests. The significant implication of this method is that it provides locational asymmetry. We find strong evidence of the EKC and PHH for China based on the empirical results of linear and nonlinear ARDL models. Similarly, findings of quantile Granger causality validate the bidirectional relationship among all variables in upper and lower quantiles. Moreover, the results of the Wald test confirm the asymmetric long-run relationship between FDI and carbon emissions (CO2). Thus, legal measures must be enhanced, accepted, rigorously imposed, and monitored in all provinces to assure a further reduction in carbon emissions. This study will be conducive for the policymakers to combat environmental contamination concerning economic growth and FDI inflow in China.

The asymmetric nexus between air pollution and COVID-19: Evidence from a non-linear panel autoregressive distributed lag model.

The emergence of a new coronavirus (COVID-19) has become a major global concern that has damaged human health and disturbing environmental quality. Some researchers have identified a positive relationship between air pollution (fine particulate matter PM2.5) and COVID-19. Nonetheless, no inclusive investigation has comprehensively examined this relationship for a tropical climate such as India. This study aims to address this knowledge gap by investigating the nexus between air pollution and COVID-19 in the ten most affected Indian states using daily observations from 9th March to September 20, 2020. The study has used the newly developed Hidden Panel Cointegration test and Nonlinear Panel Autoregressive Distributed Lag (NPARDL) model for asymmetric analysis. Empirical results illustrate an asymmetric relationship between PM2.5 and COVID-19 cases. More precisely, a 1% change in the positive shocks of PM2.5 increases the COVID-19 cases by 0.439%. Besides, the estimates of individual states expose the heterogeneous effects of PM2.5 on COVID-19. The asymmetric causality test of Hatemi-J's (2011) also suggests that the positive shocks on PM2.5 Granger-cause positive shocks on COVID19 cases. Research findings indicate that air pollution is the root cause of this outbreak; thus, the government should recognize this channel and implement robust policy guidelines to control the spread of environmental pollution.

Effects of bisphenol a on hematological, serum biochemical, and histopathological biomarkers in bighead carp (Aristichthys nobilis) under long-term exposure.

Bisphenol A (BPA) is one of the highest volume chemicals produced in the world and is frequently used in dental sealants, water bottles, food, and beverage packaging. Due to persistent applications, BPA has become a potential threat to a variety of organisms including public health. In this study, a total of 80 bighead carps were randomly placed in different four groups (A-D). Fish in groups B, C, and D were exposed to BPA @500, 1000, and 1500 µg/L, respectively for 60 days. Fish in group A served as an untreated control group. The body weight was significantly decreased while the absolute and relative weight of different visceral organs increased significantly (p < 0.05) in fish exposed to higher concentration (1500 µg/L) of BPA. Results on proximate analysis showed significantly lower values of crude proteins, lipids, and moisture contents while increased contents of ash in muscles of treated fish. The erythrocyte counts, hemoglobin concentration, lymphocytes, and monocytes significantly decreased while total leukocyte and neutrophil counts significantly increased in treated fish. Results exhibited that different serum biochemistry parameters like serum albumin and total proteins decreased significantly (p < 0.05) while alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), urea, creatinine, glucose, cholesterol, and lactate dehydrogenase (LDH) increased significantly (p < 0.05) in treated fish. Histopathological ailments like pyknosis, degeneration of glomeruli, increased Bowman's space, ceroid formation in kidneys while ceroid formation, hemorrhages, pyknosis, karyorrhexis, karyolysis, nuclear hypertrophy, and eccentric nuclei were observed in the liver of treated fish. Histological observation of different sections of the brain of treated fish exhibited degeneration of neurons in the cerebellum, lipofuscin deposition, microgliosis, necrotic neurons, inflammatory cells, and hemorrhage. Results on light microscopic observation of different sections of the heart of bighead carp revealed necrosis, inflammatory reaction, neutrophilic myocarditis, and hemorrhages. In conclusion, it is suggested that BPA induces adverse effects on physical, blood-biochemical parameters, and histopathological changes in multiple visceral tissues of exposed fish.

Dietary biomolecules as promising regenerative agents for peripheral nerve injury: An emerging nutraceutical-based therapeutic approach.

Peripheral nerve damage is a debilitating condition that can result in partial or complete functional loss as a result of axonal degeneration, as well as lifelong dependence. Many therapies have been imbued with a plethora of positive features while posing little risks. It is worth noting that these biomolecules work by activating several intrinsic pathways that are known to be important in peripheral nerve regeneration. Although the underlying mechanism is used for accurate and speedy functional recovery, none of them are without side effects. As a result, it is believed that effective therapy is currently lacking. The dietary biomolecules-based intervention, among other ways, is appealing, safe, and effective. Upregulation of transcription factors, neurotrophic factors, and growth factors such as NGF, GDNF, BDNF, and CTNF may occur as a result of these substances' dietary intake. Upregulation of the signaling pathways ERK, JNK, p38, and PKA has also been seen, which aids in axonal regeneration. Although several mechanistic approaches to understanding their involvement have been suggested, more work is needed to reveal the amazing properties of these biomolecules. We have discussed in this article that how different dietary biomolecules can help with functional recovery and regeneration after an injury. PRACTICAL APPLICATIONS: Based on the information known to date, we may conclude that treatment techniques for peripheral nerve injury have downsides, such as complications, donor shortages, adverse effects, unaffordability, and a lack of precision in efficacy. These difficulties cast doubt on their efficacy and raise severe concerns about the prescription. In this situation, the need for safe and effective therapeutic techniques is unavoidable, and dietary biomolecules appear to be a safe, cost-efficient, and effective way to promote nerve regeneration following an injury. The information on these biomolecules has been summarized here. Upregulation of transcription factors, neurotrophic factors, and growth factors, such as NGF, GDNF, BDNF, and CTNF, as well as the ERK, JNK, p38, and PKA, signaling pathways, may stimulate axonal regeneration.

Calotropis procera (leaves) supplementation exerts curative effects on promoting functional recovery in a mouse model of peripheral nerve injury.

Peripheral nerve injuries are among those complicated medical conditions, which are still waiting for their highly effective first-line therapies. In this study, the role of Calotropis procera crude leaves was evaluated at different doses for their effectiveness in improving functional recovery following sciatic nerve injury-induced in the mouse model. Thirty-two healthy albino mice were divided into four groups as Normal chow group (control, n = 8) and C. procera chow groups (50 mg/kg (n = 8), 100 mg/kg (n = 8) and 200 mg/kg (n = 8)). Behavioral analyses were performed to assess and compare improved functional recovery along with skeletal muscle mass measurement in all groups. Serum samples were analyzed for oxidative stress markers. Results showed that C. procera leaves at dose-dependent manner showed statistically prominent (p < .05) increase in sensorimotor functions reclamation as confirmed by behavioral analyses along with muscle mass restoration and prominent decline in TOS and momentous increase in TAC along with the augmented activity of antioxidative enzymes.

MicroRNA, a Promising Biomarker for Breast and Ovarian Cancer: A Review.

BACKGROUND: MicroRNAs (miRNA) belong to the substantial class of posttranscriptional gene regulators with decisive functions in typical cellular and disease progressions. They are short RNA molecules that are not translated into proteins but bind to the complementary sites of various mRNAs, thus blocking them and leading to translational inhibition. OBJECTIVE: These miRNA molecules act as signatory molecules or biomarkers for various types of malignancies. Different miRNAs are involved in different cancer-linked pathways depending on the nature, stage, and kind of cancer. The objective of this article is to discuss and review the role and significance of various miRNAs in two of the most prominent cancers; breast and ovarian cancer. METHODS: The role of miRNAs in the instigation, propagation, and metastasis of melanoma has been elucidated. RESULTS: This article focuses on the up- and down-regulation of various miRNAs in breast and ovarian cancer, with stress on diversity in their occurrence and specificity in their threshold levels in certain types and stages of cancer, suggesting their potential role as an effective diagnostic and treatment tool for cancer. CONCLUSION: Considering all the aforementioned information, it can be concluded that miRNAs can act as potential biomarkers for the diagnosis of breast and ovarian cancers.

Methanolic extract of Fennel (Foeniculum vulgare) escalates functional restoration following a compression injury to the sciatic nerve in a mouse model.

Peripheral nerve injury (PNI) is one of the major health concerns faced by the community at present. Till now, available therapeutic approaches are ineffective to fully heal a nerve injury and to assure the functional recovery entirely. Natural compounds can prove attractive and effective drug candidates to bridge up this gap. In this scenario, the present study was designed to explore the role of methanolic extract of Foeniculum vulgare (F. vulgare) seeds in accelerating the function regain following a sciatic nerve injury in a mouse model. For this purpose, 12 adult healthy albino mice (BALB/C), 8-10 weeks old, were grouped as control (Ctrl, n = 6) and treatment (Trt, n = 6). The treated group was given methanolic extract of F. vulgare (200 mg/kg per day) started from the day of nerve crush until the end of the study. The sensorimotor function regain assessed by hot plate test, grip strength, and SFI assessments was found significantly (p < .05) ameliorated in the F. vulgare-treated group. A prominent improvement in the muscle mass of the treated group further affirmed these effects. Furthermore, morphometric analysis of muscle fiber cross-sectional area of tibialis anterior muscle between groups revealed a noticeable improvement in muscle fibers' diameter of the treated group. Conclusively, these findings suggest that F. vulgare methanolic extract exhibits the potential to escalate functional recovery following a peripheral nerve injury. However, the real players of this extract and the mechanism involved in boosting functional restoration need to be dissected by further work.

Biotechnological Eminence of Chitinases: A Focus on Thermophilic Enzyme Sources, Production Strategies and Prominent Applications.

BACKGROUND: Chitin, the second most abundant polysaccharide in nature, is a constantly valuable and renewable raw material after cellulose. Due to advancement in technology, industrial interest has grown to take advantage of the chitin. OBJECTIVE: Now, biomass is being treated with diverse microbial enzymes or cells for the production of desired products under best industrial conditions. Glycosidic bonds in chitin structure are degraded by chitinase enzymes, which are characterized into number of glycoside hydrolase (GHs) families. METHODS: Thermophilic microorganisms are remarkable sources of industrially important thermostable enzymes, having ability to survive harsh industrial processing conditions. Thermostable chitinases have an edge over mesophilic chitinases as they can hydrolyse the substrate at relatively high temperatures and exhibit decreased viscosity, significantly reduced contamination risk, thermal and chemical stability and increased solubility. Various methods are employed to purify the enzyme and increase its yield by optimizing various parameters such as temperature, pH, agitation, and by investigating the effect of different chemicals and metal ions etc. Results: Thermostable chitinase enzymes show high specific activity at elevated temperature which distinguish them from mesophiles. Genetic engineering can be used for further improvement of natural chitinases, and unlimited potential for the production of thermophilic chitinases has been highlighted due to advancement in synthetic biological techniques. Thermostable chitinases are then used in different fields such as bioremediation, medicine, agriculture and pharmaceuticals. CONCLUSION: This review will provide information about chitinases, biotechnological potential of thermostable enzyme and the methods by which they are being produced and optimized for several industrial applications. Some of the applications of thermostable chitinases have also been briefly described.

Evaluation of Oxidative stress, antioxidant enzymes and genotoxic potential of bisphenol A in fresh water bighead carp (Aristichthys nobils) fish at low concentrations.

Bisphenol A (BPA) is one of the emerging contaminants associated with deleterious health effects on both public and wildlife and is extensively incorporated into different industrial products. Therefore, the current trial was conducted to determine the oxidative stress, status of different antioxidant enzymes and genotoxic potential of bisphenol A in fresh water fish at low concentrations. For this purpose, a total of 80 fresh water bighead carp (Aristicthys nobilis) received from commercial fish center were randomly divided and kept in four groups (A-D). Fish in groups (B-D) were exposed to different levels of BPA for a period of 60 days while fish of group A served as control group. Treated fish exhibited different physical and behavioral ailments in a time and treatment manners. Results showed significantly (p < 0.05) increased quantity of different oxidative stress biomarkers such as thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH) and the contents of reactive oxygen species (ROS) in gills, liver, kidneys and brain of exposed fish. Concentration of different antioxidant enzymes like catalase, superoxide dismutase, peroxidase and total proteins was significantly (p < 0.05) decreased in gills, liver, kidneys and brain of exposed fish. Results showed significantly (p < 0.05) increased frequency of morphological alterations, nuclear changes in red blood cells and increased DNA damage potential of bisphenol A in gills, liver, kidneys and brain tissues. The current trial concludes that even at very low concentrations bisphenol A causes toxic effects via turbulences in physiological and biochemical parameters in multiple tissues of fish.

Asymmetric effects of energy efficiency and renewable energy on carbon emissions of BRICS economies: evidence from nonlinear panel autoregressive distributed lag model.

Embracing energy efficiency (EE) and renewable energy (RE) is essential for improving environmental quality. This research investigates the asymmetric impacts of EE, RE, and other factors on CO2 emissions in BRICS (i.e., Brazil, Russia, India, China, and South Africa) countries from 1990 to 2014. In contrast to previous studies, the present study considers EE as a major cause of CO2 emissions in BRICS countries. By using the new hidden panel cointegration and nonlinear panel autoregressive distributive lag model, this study is the first of its kind that unfolds the asymmetric links among EE, RE, and CO2 emissions. Findings clearly explain that the impact of the selected variables on CO2 emissions is asymmetric, and both EE and RE help to lower CO2 emissions in BRICS countries. In the long run, positive shocks in EE and RE can significantly mitigate CO2 emissions in BRICS economies. In particular, a 1% fluctuation in the positive sum of EE reduces CO2 emissions by 0.783% in the long run. On the other hand, a 1% fluctuation in the positive component of RE reduces CO2 emissions by 0.733%. Moreover, individual country estimates suggest the heterogeneous effects among BRICS countries. Based on the empirical findings, policymakers should consider the asymmetric behavior of the EE, RE, and economic growth while formulating, energy, environment, and growth policies of BRICS countries. Graphical abstract.

Primary intracranial malignant melanoma.

Primary intracranial melanoma is an extremely rare lesion of the brain. A 28 years old lady, without any co-morbid conditions, presented with headache and left side facial numbness. MRI of brain showed a mass lesion in left middle cranial fossa extending into posterior fossa, with signals characteristics of melanoma. Histology and immunohistochemistry confirmed the diagnosis after surgical excision of that lesion. Patient remained symptom-free till the last follow-up that was four years postoperatively.